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We firstly authenticated that oral pinocembrin (PIN) administration obviously mitigated tissue damage and renal dysfunction induced by I\/R injury, and PIN attenuated UUO\u2010caused RF, as confirmed by the reduced expression of fibrotic markers as well as hematoxylin\u2013eosin (H&amp;E), Sirius red, immunohistochemistry, and Masson staining. Meanwhile, the beneficial role of PIN was again demonstrated in HK\u20102 cells with hypoxia\u2013reoxygenation (H\/R) or transforming growth factor beta\u20101 (TGF\u2010\u03b21) treatment. Importantly, the \u201cingredient\u2013target\u2013pathway\u2013disease\u201d network was established through bioinformatics analysis and molecular docking, which showed that PIN may target cytochrome P450 1B1 (CYP1B1) and modulate the mitogen\u2010activated protein kinase (MAPK) pathway to exert its impact during injury. Furthermore, experiments confirmed that PIN usage remarkably constrained CYP1B1 expression, reactive oxygen species (ROS) production, MAPK\u2010pathway\u2010associated inflammation, or apoptosis during I\/R injury or UUO exposure. PIN also ameliorated the elevated protein phosphorylation of MAPK pathway components [p38, extracellular signal\u2010regulated kinase (ERK) and c\u2010Jun N\u2010terminal kinase 1 (JNK ERK and JNK)], which validated the PIN\u2010induced inhibition of the MAPK signaling pathway in renal I\/R or UUO injury. Moreover, the AAV9 (adeno\u2010associated virus 9)\u2010packed CYP1B1 or pcDNA\u2010CYP1B1 overexpression plasmid was utilized to treat C57BL\/6 mice or HK\u20102 cells to overexpress CYP1B1, respectively. Notably, CYP1B1 overexpression considerably abolished PIN's restriction impact on ROS generation and MAPK pathway activation. In conclusion, via bioinformatics analysis, molecular docking, animal model, and cellular experiments, we proved that PIN alleviates renal I\/R injury\/UUO\u2010generated renal fibrosis through regulating the CYP1B1\/ROS\/MAPK axis.<\/jats:p>","DOI":"10.1111\/febs.17414","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:04:46Z","timestamp":1738109086000},"page":"2119-2144","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pinocembrin alleviates renal ischemia\u2013reperfusion injury\/unilateral ureteral obstruction (<scp>UUO<\/scp>)\u2010generated renal fibrosis by targeting the <scp>CYP1B1<\/scp>\/<scp>ROS<\/scp>\/<scp>MAPK<\/scp> axis"],"prefix":"10.1111","volume":"292","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4367-901X","authenticated-orcid":false,"given":"Bang\u2010Hua","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Urology Renmin 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